Hypoxic pulmonary vasoconstriction: mechanisms of oxygen-sensing

A. Mark Evans, D. Grahame Hardie, Chris Peers, Amira Mahmoud

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    Abstract

    Purpose of review

    Hypoxic pulmonary vasoconstriction (HPV) is driven by the intrinsic response to hypoxia of pulmonary arterial smooth muscle and endothelial cells. These are representatives of a group of specialized O-2-sensing cells, defined by their acute sensitivity to relatively small changes in pO(2), which have evolved to modulate respiratory and circulatory function in order to maintain O-2 supply within physiological limits. The aim of this article is to discuss recent investigations into the mechanism(s) of hypoxia-response coupling and, in light of these, provide a critical assessment of current working hypotheses.

    Recent findings

    Upon exposure to hypoxia state-of-the-art technologies have now confirmed that mitochondrial oxidative phosphorylation is inhibited in all O-2-sensing cells, including pulmonary arterial smooth muscle cells. Thereafter, evidence has been presented to indicate a role as principal effector for the 'gasotransmitters' carbon monoxide and hydrogen sulphide, reactive oxygen species or, in marked contrast, reduced cellular redox couples. Considering recent evidence in favour and against these proposals we suggest that an alternative mechanism may be key, namely the activation of adenosine monophosphate-activated protein kinase consequent to inhibition of mitochondrial oxidative phosphorylation.

    Summary

    HPV supports ventilation-perfusion matching in the lung by diverting blood flow away from oxygen-deprived areas towards regions rich in O-2. However, in diseases such as emphysema and cystic fibrosis, widespread HPV leads to hypoxic pulmonary hypertension and ultimately right heart failure. Determining the precise mechanism(s) that underpins hypoxia-response coupling will therefore advance understanding of the fundamental processes contributing to related pathophysiology and provide for improved therapeutics.

    Original languageEnglish
    Pages (from-to)13-20
    Number of pages8
    JournalCurrent Opinion in Anaesthesiology
    Volume24
    Issue number1
    DOIs
    Publication statusPublished - Feb 2011

    Keywords

    • AMPK
    • CO
    • H2S
    • HO-2
    • hypoxia
    • pulmonary artery
    • redox
    • ROS
    • ACTIVATED PROTEIN-KINASE
    • CAROTID-BODY CHEMORECEPTOR
    • ARTERY SMOOTH-MUSCLE
    • ADRENOMEDULLARY CHROMAFFIN CELLS
    • CYCLIC ADP-RIBOSE
    • HEME OXYGENASE-2
    • RAT PULMONARY
    • I CELLS
    • MITOCHONDRIAL INHIBITORS
    • O-2-SENSING CELLS

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